Introduction

Progressive tremor and profound functional decline during pregnancy demand careful neurologic localization. In this case, a detailed history and recognition of Kayser–Fleischer rings provided the decisive clues to a treatable inherited disorder despite major diagnostic and geographic barriers.

Clinical Case

A 30-year-old gravida 5, para 4 Karen woman traveled for more than 5 hours to reach a clinic serving a conflict-affected region of Myanmar. For approximately 1 year, she had experienced progressively worsening muscle cramps followed by tremor involving both the upper and lower extremities.

Her functional decline had become profound. By the time of presentation, she could no longer walk, stand, or sit without assistance. Her mother, husband, and children carried her to the bathroom and provided food and water. Her voice had become quiet, she appeared withdrawn, and she had lost weight during her current pregnancy.

Her gestational age was approximately 7 months, confirmed by a late ultrasound. Her previous pregnancies had been uncomplicated, and she had delivered her children at home. She did not consume alcohol.

The family had previously sought care at two hospitals but had been told that nothing could be done. Further questioning revealed that the patient’s sister had developed a similar progressive tremor and had died at 20 years of age following a respiratory infection.

First Teaching Pause: Defining the Syndrome

Before assigning a diagnosis, the presentation should be converted into a neurologic syndrome.

This patient had a chronic, progressive, bilateral movement disorder characterized primarily by severe postural and intention tremor. Her disability was not explained by weakness: she required assistance with nearly every activity, but this functional dependence appeared to result from impaired motor control rather than loss of muscle power.

The quiet voice, reduced facial expression, delayed visual tracking, and withdrawal raised the possibility of additional extrapyramidal or neuropsychiatric involvement. The preserved strength, sensation, and reflexes argued against a primary peripheral neuropathy, myopathy, spinal cord disorder, or motor neuron disease.

The combination can therefore be summarized as:

A progressive, predominantly extrapyramidal and cerebellar-appearing movement disorder in a young woman, with possible psychiatric involvement and a family history suggesting an inherited disease.

Pregnancy was clinically important, but it should not be assumed to explain the neurologic syndrome.

Initial Differential Diagnosis

The differential diagnosis for progressive tremor and loss of motor independence in a young adult is broad. The patient’s age, family history, and chronic progression made an inherited or metabolic disorder particularly important.

Wilson’s disease

Wilson’s disease should be considered early in any young patient with otherwise unexplained tremor, dystonia, parkinsonism, dysarthria, psychiatric change, or mixed movement abnormalities. It can produce major neurologic disability with relatively subtle hepatic findings.

The family history of a similarly affected young sister supported an autosomal recessive disorder, although a family history alone would not establish the diagnosis.

Hereditary or degenerative movement disorders

Hereditary spinocerebellar ataxia, juvenile parkinsonism, Huntington disease, hereditary dystonia, and other genetic movement disorders could cause progressive disability. However, the patient’s tremor was not accompanied by a clearly described cerebellar gait syndrome, chorea, upper motor neuron findings, or a dominant inheritance pattern.

Structural disease

A lesion affecting the cerebellum, brainstem, basal ganglia, or thalamus could cause tremor and impaired coordination. A structural lesion would be less likely to explain a similarly affected sibling unless an underlying inherited syndrome predisposed both individuals.

Toxic or metabolic disease

Thyroid disease, medication or toxin exposure, vitamin deficiency, electrolyte disturbance, and hepatic or renal dysfunction could produce tremor or altered motor control. The prolonged progression and family history made an acquired metabolic disturbance less compelling, but basic laboratory investigation remained necessary.

Autoimmune or infectious disease

Autoimmune encephalitis, postinfectious disorders, human immunodeficiency virus–associated disease, and chronic central nervous system infection could cause mixed neurologic and psychiatric manifestations. The 1-year course without fever, encephalopathy, seizures, or focal deficits reduced—but did not eliminate—these possibilities.

Pregnancy-related neurologic disease

Pregnancy introduces additional considerations, including eclampsia, cerebral venous thrombosis, stroke, thyroid disease, nutritional deficiency, and medication-related effects. These disorders generally would not account for the preceding year of progressive tremor or the similarly affected sister.

Neurologic Examination and the Diagnostic Pivot

Examination demonstrated marked bilateral postural and intention tremor, worse on the left. Strength was preserved throughout. There was no muscle wasting, and reflexes and sensation were normal. Coordination testing was limited primarily by the severity of the tremor.

The patient had reduced facial expression and hypophonia without clearly slurred speech. Her vision was grossly intact, although she followed objects with some delay. There was no nystagmus.

The examination of her eyes revealed bilateral Kayser–Fleischer rings.

The remainder of the systemic examination showed mild palmar erythema but no palpable hepatomegaly or other overt signs of chronic liver disease.

Second Teaching Pause: Why the Eye Examination Matters

The bilateral corneal rings represented the principal diagnostic pivot.

Kayser–Fleischer rings result from copper deposition in Descemet’s membrane of the cornea. In a young patient with an unexplained movement disorder, their presence substantially raises the probability of Wilson’s disease.

The finding did not merely add another item to the differential. It reorganized the differential around a unifying disorder capable of explaining:

• The progressive tremor
• Hypomimia and hypophonia
• Possible psychiatric or behavioral change
• Young age
• Similar illness in a sibling
• Potential hepatic biochemical abnormalities
• Reproductive and pregnancy-related manifestations

This was particularly important in a setting where neuroimaging and specialist diagnostic services were difficult to obtain. The decisive information came from direct examination rather than advanced technology.

Diagnostic Evaluation

Laboratory investigation showed mild anemia, with a hemoglobin concentration of 9.7 g/dL. Liver testing demonstrated only modest abnormalities: aspartate aminotransferase was 37 U/L, alkaline phosphatase 137 U/L, and gamma-glutamyl transferase 69 U/L. Bilirubin was normal. Testing for human immunodeficiency virus and hepatitis B and C was negative.

The absence of severe liver dysfunction did not argue strongly against Wilson’s disease. Neurologic Wilson’s disease may be clinically prominent despite limited biochemical evidence of hepatic injury.

Copper studies provided strong diagnostic evidence:

• Serum ceruloplasmin: 0.091 g/L, below the reported reference range of 0.2–0.6 g/L
• 24-hour urinary copper excretion: 2325 μg/day, markedly above the reported normal value of less than 35 μg/day

Six months after presentation, genetic analysis demonstrated a homozygous pathogenic ATP7B variant, c.2692C>T (p.Gln898*), confirming Wilson’s disease.

Evolving Clinical Reasoning

The diagnostic process can be reconstructed as a sequence of probability-changing observations.

Stage 1: Progressive tremor in a young woman

At this stage, the differential remained broad. The chronic progression suggested a degenerative, inherited, metabolic, toxic, or structural disorder rather than an acute pregnancy-related complication.

Stage 2: Preserved strength and sensation

The patient’s inability to walk or feed herself could initially be misinterpreted as generalized weakness. Examination showed that strength was preserved. Her disability resulted primarily from severe tremor and impaired motor control, localizing the syndrome to central motor networks rather than peripheral nerve, muscle, or neuromuscular junction.

Stage 3: A similarly affected sister

The sister’s history raised suspicion for an inherited disorder. Because Wilson’s disease is autosomal recessive, affected siblings may occur despite unaffected parents.

Stage 4: Kayser–Fleischer rings

The corneal finding sharply increased the likelihood of Wilson’s disease and justified directed copper testing.

Stage 5: Copper studies

Markedly low ceruloplasmin and profoundly elevated urinary copper provided strong biochemical support for the clinical diagnosis.

Stage 6: ATP7B testing

Identification of a homozygous pathogenic ATP7B variant confirmed the diagnosis.

The case therefore illustrates a classical progression from syndrome recognition to targeted bedside examination, biochemical corroboration, and eventual molecular confirmation.

Final Diagnosis

Neurologic Wilson’s disease presenting during late pregnancy with severe tremor, hypomimia, hypophonia, and profound functional dependence.

The patient had comparatively limited clinical and biochemical hepatic involvement despite advanced neurologic manifestations.

Diagnostic Discussion

Wilson’s disease is an autosomal recessive disorder of copper metabolism caused by pathogenic variants in ATP7B. Impaired biliary copper excretion results in progressive copper accumulation, particularly in the liver, brain, and cornea.

The neurologic phenotype is heterogeneous. Patients may develop tremor, dystonia, dysarthria, dysphagia, parkinsonism, incoordination, behavioral change, depression, anxiety, or combinations of these manifestations. The patient’s postural and intention tremor, hypomimia, hypophonia, and withdrawn appearance were therefore compatible with a mixed neurologic Wilson’s disease phenotype.

An important lesson is that the extent of neurologic disease does not necessarily parallel the apparent severity of hepatic disease. This patient had lost nearly all motor independence, yet she had no hepatomegaly, jaundice, decompensated cirrhosis, or major bilirubin abnormality. Her liver enzyme abnormalities were mild.

The pregnancy was also unusual. The authors noted that menstrual disturbance, impaired conception, and miscarriage may occur in Wilson’s disease and that successful pregnancy in untreated patients with major symptoms is uncommon. In this case, severe neurologic disease coexisted with a viable late pregnancy and ultimately a favorable neonatal outcome.

Management Discussion

Treatment initially consisted of a low-copper diet and oral zinc sulfate at 30 mg three times daily. Zinc reduces intestinal copper absorption and was more readily obtainable in the resource-limited setting.

D-penicillamine subsequently became available and was initiated at 250 mg once daily together with pyridoxine 20 mg twice daily. The dose of D-penicillamine was later adjusted, reaching a maximum reported daily dose of 875 mg.

At 39 weeks and 1 day of gestation, approximately 2 weeks after D-penicillamine was started, the patient delivered a 3010-g female infant by vaginal breech delivery. Apgar scores were 9 and 10 at 5 and 10 minutes. No abnormality was identified on the reported newborn surface examination.

The mother wished to breastfeed but initially required another person to position and support the infant because her tremor prevented her from holding the child safely.

The therapeutic decision required balancing several considerations:

• Severity of the maternal neurologic disease
• Gestational age at treatment initiation
• Availability and affordability of medications
• Potential fetal and neonatal effects
• Maternal preference to breastfeed
• Feasibility of long-term monitoring in a conflict zone

The source report states that D-penicillamine has been associated with teratogenic risk, although the late gestational age at initiation reduced concern for major organogenesis-related effects in this case. The authors also considered zinc and D-penicillamine compatible with breastfeeding. Their long-term plan was to transition the patient to lifelong zinc monotherapy.

Outcome and Follow-Up

At 2 months postpartum, the patient’s symptoms had improved sufficiently for her to walk without assistance.

After 1 year and 5 months of follow-up, she had experienced substantial neurologic improvement while receiving D-penicillamine, pyridoxine, and zinc. Her infant remained healthy.

The four surviving children underwent serum ceruloplasmin testing and 24-hour urinary copper assessment. The results were considered unlikely to indicate Wilson’s disease, although the children remained under follow-up.

Follow-up could not be performed at the conventional frequency because travel within the conflict zone was dangerous and expensive. Intervals between in-person visits extended to as long as 6 months.

The improvement was clinically meaningful. A patient who had been unable to sit, walk, eat, drink, or care for herself regained the ability to ambulate and participate in the care of her infant and family.

CARE Timeline

Cognitive Pitfalls

Anchoring on pregnancy

Pregnancy may invite premature attribution of tremor, fatigue, weight change, or functional deterioration to gestational physiology or obstetric complications. The neurologic symptoms in this case began well before late pregnancy and progressed over approximately 1 year.

Equating dependence with weakness

The patient could not walk or feed herself, but formal examination showed preserved strength. Severe movement disorders can cause profound functional dependence without paralysis.

Excluding Wilson’s disease because liver disease is subtle

The absence of jaundice, hepatomegaly, or decompensated cirrhosis does not exclude neurologic Wilson’s disease.

Failure to obtain a multigenerational family history

The sister’s similar illness and early death were critical clues. A family history may be particularly valuable where prior medical records and advanced testing are unavailable.

Failure to examine the eyes

The Kayser–Fleischer rings transformed the diagnostic assessment. Omitting the ocular examination could have resulted in continued diagnostic delay.

Therapeutic nihilism

The family had previously been told that nothing could be done. Even advanced neurologic Wilson’s disease may improve substantially with copper-directed therapy, although individual outcomes vary.

Resource-Limited and Conflict-Affected Care

The prolonged diagnostic delay was not simply a failure of disease recognition. It reflected structural barriers including distance, cost, insecurity, disrupted healthcare infrastructure, and limited access to specialists and medication.

The patient reached the treating clinic only after traveling more than 5 hours. The same barriers complicated subsequent monitoring, producing follow-up intervals of up to 6 months despite the need for close surveillance during D-penicillamine treatment.

The authors emphasized that the patient’s sister may have remained undiagnosed for similar reasons. In this context, bedside skills acquired added importance. A thorough neurologic and ocular examination created a rational pathway toward targeted testing and treatment when comprehensive diagnostic resources were not immediately accessible.

Clinical Pearls

1. Consider Wilson’s disease in every young patient with an unexplained movement disorder. Tremor, dystonia, parkinsonism, dysarthria, behavioral change, and psychiatric symptoms may occur in varying combinations.
2. Functional dependence does not necessarily indicate weakness. Severe tremor and impaired motor control may prevent walking, eating, or self-care despite preserved power.
3. Examine the corneas. Kayser–Fleischer rings may provide the central diagnostic clue in neurologic Wilson’s disease.
4. Minimal hepatic findings do not exclude advanced neurologic disease. Neurologic and hepatic manifestations may be markedly discordant.
5. Family history is diagnostically valuable. A similarly affected sibling should raise concern for an inherited metabolic disorder.
6. Do not delay directed therapy solely while awaiting genetic confirmation. In this case, the clinical examination and copper studies provided sufficient evidence to begin treatment before molecular results became available.
7. Pregnancy does not exclude Wilson’s disease. Although reproductive dysfunction may occur, symptomatic patients can become pregnant and may achieve favorable outcomes with individualized management.
8. Resource limitations change implementation, not diagnostic principles. Careful history-taking, localization, and physical examination remain foundational.

Clinical Take-Home Message

Wilson’s disease should be considered in any young adult with a progressive tremor or mixed movement disorder, particularly when psychiatric features or a suggestive family history are present. In this patient, preserved strength clarified that profound functional dependence resulted from disordered motor control rather than paralysis. Recognition of bilateral Kayser–Fleischer rings focused the investigation, and low ceruloplasmin, markedly elevated urinary copper, and a homozygous pathogenic ATP7B variant established the diagnosis.

The case also demonstrates that severe neurologic disability may coexist with only modest hepatic biochemical abnormalities and that meaningful recovery may occur after copper-directed treatment. Most importantly, it shows how disciplined bedside clinical reasoning can lead to life-changing treatment even when conflict, poverty, transportation barriers, and limited diagnostic resources constrain care.

Board-Style Questions

Question 1

A 30-year-old pregnant woman develops progressive bilateral tremor, hypophonia, reduced facial expression, and an inability to walk without assistance. Strength, sensation, and reflexes are normal. Her sister died at age 20 after developing similar symptoms. Which diagnosis should receive the highest priority?

A. Guillain–Barré syndrome
B. Wilson’s disease
C. Myasthenia gravis
D. Eclampsia
E. Essential tremor

Correct answer: B. Wilson’s disease

Explanation: The patient has a chronic progressive movement disorder rather than weakness. Her young age, mixed tremor and parkinsonian features, behavioral change, and similarly affected sibling strongly suggest an inherited metabolic disorder. Wilson’s disease is particularly important because it is treatable and may present with tremor, dystonia, parkinsonism, dysarthria, or psychiatric symptoms.

Why the other options are incorrect: Guillain–Barré syndrome causes progressive weakness and areflexia, neither of which was present. Myasthenia gravis causes fatigable weakness rather than severe postural and intention tremor. Eclampsia is associated with hypertension, seizures, and acute obstetric illness rather than a 1-year progressive movement disorder. Essential tremor may be familial but would not adequately explain hypomimia, profound loss of motor independence, possible behavioral change, and Kayser–Fleischer rings.

Teaching pearl: In a young adult with an unexplained movement disorder, Wilson’s disease should be excluded before the syndrome is labeled degenerative or idiopathic.

Question 2

Which examination finding most directly narrowed the differential diagnosis in this patient?

A. Mild palmar erythema
B. Hypophonia
C. Asymmetric intention tremor
D. Bilateral Kayser–Fleischer rings
E. Weight loss during pregnancy

Correct answer: D. Bilateral Kayser–Fleischer rings

Explanation: Kayser–Fleischer rings reflect copper deposition in Descemet’s membrane. In a young patient with progressive neurologic symptoms, their presence strongly supports Wilson’s disease and should lead to directed copper studies.

Why the other options are incorrect: Palmar erythema may occur during pregnancy and is nonspecific. Hypophonia can occur in several extrapyramidal disorders. Asymmetric intention tremor suggests dysfunction of central motor pathways but is not disease-specific. Weight loss is clinically concerning but has a broad differential.

Teaching pearl: A focused ocular examination can sometimes provide more diagnostic value than an extensive but nondirected laboratory panel.

Question 3

Which combination of findings most strongly supports Wilson’s disease in this case?

A. Elevated ceruloplasmin and reduced urinary copper
B. Normal ceruloplasmin and elevated bilirubin
C. Reduced ceruloplasmin and markedly elevated 24-hour urinary copper
D. Reduced ceruloplasmin and reduced urinary copper
E. Elevated serum copper and normal urinary copper

Correct answer: C. Reduced ceruloplasmin and markedly elevated 24-hour urinary copper

Explanation: The patient’s ceruloplasmin was 0.091 g/L, below the reported reference range, and her 24-hour urinary copper excretion was 2325 μg/day, far above the reported normal value. In the clinical context, these findings provided strong biochemical support for Wilson’s disease.

Why the other options are incorrect: Elevated ceruloplasmin would not support the typical biochemical pattern. Reduced urinary copper would be inconsistent with increased copper excretion associated with untreated Wilson’s disease. Bilirubin may be normal, particularly when neurologic disease predominates. Serum copper values alone may be difficult to interpret and were not the decisive measurements in this case.

Teaching pearl: Copper studies must be interpreted together with phenotype and examination findings rather than in isolation.

Question 4

The patient cannot walk, sit, eat, or drink without help, but strength and reflexes are normal. Which interpretation is most accurate?

A. The examination is internally inconsistent
B. Her disability is caused primarily by impaired motor control
C. She has a severe peripheral neuropathy
D. She has a neuromuscular junction disorder
E. Her symptoms are most likely psychogenic

Correct answer: B. Her disability is caused primarily by impaired motor control

Explanation: Severe tremor, dystonia, ataxia, or parkinsonism can produce extreme disability despite preserved strength. The patient’s inability to perform daily activities reflected loss of coordinated and controlled movement rather than failure of force generation.

Why the other options are incorrect: Peripheral neuropathy would usually produce sensory loss, distal weakness, or reflex abnormalities. A neuromuscular junction disorder would produce fatigable weakness. The examination was coherent with a severe central movement disorder. The presence of objectively documented tremor, Kayser–Fleischer rings, abnormal copper studies, and an ATP7B variant argues strongly against a psychogenic explanation.

Teaching pearl: “Unable to walk” is a functional description, not a localization. The examiner must determine whether the cause is weakness, ataxia, tremor, dystonia, pain, sensory loss, or impaired consciousness.

Question 5

Which statement best captures the principal diagnostic lesson of this case?

A. Advanced neuroimaging is required before Wilson’s disease can be suspected
B. Severe neurologic Wilson’s disease invariably produces decompensated cirrhosis
C. Genetic confirmation must be obtained before treatment is started
D. Careful history and physical examination can direct diagnosis even where resources are limited
E. Pregnancy makes Wilson’s disease clinically implausible

Correct answer: D. Careful history and physical examination can direct diagnosis even where resources are limited

Explanation: The history established a chronic inherited-appearing movement disorder, and ocular examination identified Kayser–Fleischer rings. These findings directed appropriate copper testing and treatment before genetic confirmation became available.

Why the other options are incorrect: Neuroimaging may contribute to evaluation but was not required to recognize the syndrome in this case. Neurologic disease may be severe despite limited hepatic manifestations. Genetic testing confirmed the diagnosis but was obtained 6 months after presentation; treatment had already begun based on clinical and biochemical evidence. Pregnancy does not exclude Wilson’s disease, although untreated symptomatic pregnancy is uncommon.

Teaching pearl: Resource limitations increase the value of disciplined clinical reasoning; they do not diminish it.

Journal of Medical Case Reports is the world’s first international, PubMed-listed, medical journal devoted to publishing case reports from all medical disciplines and will consider any original case report that expands the field of general medical knowledge, and original research relating to case reports. The journal is open access, and strongly endorses the CARE guidelines for case reports, requiring authors to submit populated CARE checklists with submissions to improve transparency in reporting.